The training of quantitative basic scientists in clinically-related imaging science is increasingly important. Excellent imaging sciences are well represented at Penn in multiple schools, but no formal integration of efforts in graduate training existed, nor was there a formal clinical component to the training until the creation of the Training Program in Biomedical Imaging and Informational Sciences. Established in 2006 under the auspices of the HHMI-NIBIB Interfaces Initiative, the program represents a partnership led by the Institute for Medicine and Engineering and the Department of Radiology in collaboration with many other Departments across multiple Schools. Our premise is that the most successful research and technologies in quantitative imaging science are those that integrate clinical relevance, mathematical rigor, and engineering finesse. Accordingly, the program embraces strong clinical exposure alongside analytical imaging science. The objective is to develop a new kind of interdisciplinary training by ensuring that students attain a level of integration that woud allow them to become the next generation of leaders in hypothesis-driven, clinically focused biomedical imaging research. Program outcomes to date are strong across all impact measures, indicating successful progress toward training objectives: publications (107); numerous research awards and distinctions; and recruitment of 6 URM and disadvantaged trainees. A formalized curriculum, the doctoral foundation, developed for the program provides 18 months of vertical integration of the core didactic elements of biomedicine and basic science education in biomedical imaging through 4 components, two of them Foundational, followed by Integrative and Professional components. In the first, Foundations in Biomedical Science (2 courses), students participate in modified modules 1 and 2 of the medical student curriculum that teaches the Core Principles of Medicine (including Gross Anatomy) and a 12- month sequence of organ systems medicine, Integrative Systems and Diseases. This is complemented by 4 courses in Foundations of Imaging Science: Molecular Imaging, Biomedical Image Analysis, Fundamental Techniques of Imaging, and Mathematics of Medical Imaging & Measurements. The third component is an Integrative Module: Advanced Biomedical Imaging Applications and Biomedical Image Sciences Seminars. The fourth component is Professional Training: Responsible Conduct of Research, Teaching Practicum, Patient-Oriented Research Training, Research 'Survival' Skills, and Career Development Skills. The core curriculum is complemented by many elective courses offered through the program faculty and tailored to Biomedical Imaging. Obligatory Laboratory Rotations will be offered through the laboratories of the participating faculty. To ensure that the thesis research is directed to translational medicine through the solution of discrete clinical problems, trainees will be co-advised by members of the clinical and basic science faculty.